[1S-[1.alpha.,2.alpha.(Z), 3.alpha.,4.alpha.[[-7- [3-[[[[1-Oxoheptyl)-amino]acetyl]amino]methyl]-7-oxabicyclo-[2.2.1]hept-2- yl]-5-heptenoic acid is a cardiovascular agent useful, for example, in the treatment of thrombotic disease. U.S. Pat. No. 4,663,336, issued on May 5, 1987, describes a synthesis of this compound that begins with [1S-[1.alpha.,2.alpha.(Z), 3.alpha., 4.alpha.]]-7-[3-Hydroxymethyl-7-oxabicyclo-[2.2.1]-hept-2-yl]-5-heptenoic acid. Preparation of this latter compound is described in U.S. Pat. No. 4,143,054.
In the latter patent, furan and maleic anhydride react in ether solution to form compound A in Reaction Scheme 1. Compound A is reduced to form compound B, which is then reduced by, for example, a borohydride in tetrahydrofuran to form compound C. Compound C is then treated with diisobutylaluminium hydride or diisobutylborane to form compound D in racemic form.
Compound D may be resolved chemically (e.g., with d-menthol and Amberlyst.RTM. in methylene chloride) but with yields of less than 50% of the desired (-) optical enantiomer. Moreover, the compound C-to-D conversion may be dangerous in a large scale process.